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Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells

Raska, Milan ; Moldoveanu, Zina ; Suzuki, Hitoshi ; Brown, Rhubell ; Kulhavy, Rose ; Andrasi, Judit ; Hall, Stacy ; Vu, Huong L ; Carlsson, Fredric LU orcid and Lindahl, Gunnar LU , et al. (2007) In Journal of Molecular Biology 369(1). p.69-78
Abstract
Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level.... (More)
Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level. Expression of the ST6-GalNAcII gene and activity of the CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase were higher in IgA1-producing cell lines from IgAN patients than in such cells from healthy controls. These data are the first evidence that human cells that lack ST6-GalNAcI can sialylate core 1 GalNAc-Ser/Thr. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Journal of Molecular Biology
volume
369
issue
1
pages
69 - 78
publisher
Elsevier
external identifiers
  • pmid:17418236
  • wos:000246661100006
  • scopus:34247394150
ISSN
1089-8638
DOI
10.1016/j.jmb.2007.03.002
language
English
LU publication?
yes
id
1f0a1477-7b6c-49e4-be0d-787c2735d5f6 (old id 1137733)
date added to LUP
2016-04-01 16:43:55
date last changed
2024-10-12 02:30:12
@article{1f0a1477-7b6c-49e4-be0d-787c2735d5f6,
  abstract     = {{Glycosylation defects occur in several human diseases. In IgA nephropathy, IgA1 contains O-glycans that are galactose-deficient and consist mostly of core 1 alpha2,6 sialylated N-acetylgalactosamine, a configuration suspected to prevent beta1,3 galactosylation. We confirmed the same aberrancy in IgA1 secreted by the human DAKIKI B cell line. Biochemical assays indicated CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase activity in this cell line. However, a candidate enzyme, ST6-GalNAcI, was not transcribed in DAKIKI cells, B cells isolated from blood, or Epstein-Barr virus (EBV)-immortalized IgA1-producing cells from the blood of IgAN patients and healthy controls. Instead, ST6-GalNAcII transcription was detected at a high level. Expression of the ST6-GalNAcII gene and activity of the CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase were higher in IgA1-producing cell lines from IgAN patients than in such cells from healthy controls. These data are the first evidence that human cells that lack ST6-GalNAcI can sialylate core 1 GalNAc-Ser/Thr.}},
  author       = {{Raska, Milan and Moldoveanu, Zina and Suzuki, Hitoshi and Brown, Rhubell and Kulhavy, Rose and Andrasi, Judit and Hall, Stacy and Vu, Huong L and Carlsson, Fredric and Lindahl, Gunnar and Tomana, Milan and Julian, Bruce A and Wyatt, Robert J and Mestecky, Jiri and Novak, Jan}},
  issn         = {{1089-8638}},
  language     = {{eng}},
  number       = {{1}},
  pages        = {{69--78}},
  publisher    = {{Elsevier}},
  series       = {{Journal of Molecular Biology}},
  title        = {{Identification and characterization of CMP-NeuAc:GalNAc-IgA1 alpha2,6-sialyltransferase in IgA1-producing cells}},
  url          = {{http://dx.doi.org/10.1016/j.jmb.2007.03.002}},
  doi          = {{10.1016/j.jmb.2007.03.002}},
  volume       = {{369}},
  year         = {{2007}},
}